| 1. |
Harada, T.*, Kikushige, Y.*, Miyamoto, T., Uno, K., Niiro, H., Kawakami, A., Koga, T., Akashi, K. & Yoshizaki, K. , Peripheral helper-T-cell-derived CXCL13 is a crucial pathogenic factor in idiopathic multicentric Castleman disease, Nature Communications, 2023.12. |
| 2. |
Kikushige, Y., Miyamoto, T., Kochi, Y., Semba, Y., Ohishi, M., Irifune, H., Hatakeyama, K., Kunisaki, Y., Sugio, T., Sakoda, T., Miyawaki, K., Kato, K., Soga, T. & Akashi, K., Human acute leukemia utilizes branched-chain amino acid catabolism to maintain stemness through regulating PRC2 function, Blood Advances, 10.1182/bloodadvances.2022008242, 2022.07. |
| 3. |
Taro Tochigi, Toshihiro Miyamoto, Kiwamu Hatakeyama, Teppei Sakoda, Daisuke Ishihara, Hidetoshi Irifune, Takahiro Shima, Koji Kato,
Takahiro Maeda, Takumi Ito, Hiroshi Handa, Koichi Akashi, and Yoshikane Kikushige, Aromatase is a novel neosubstrate of cereblon responsible for immunomodulatory drug–induced thrombocytopenia, Blood, 2020.06. |
| 4. |
Yoshikane Kikushige, Toshihiro Miyamoto, Junichiro Yuda, Siamak Jabbarzadeh-Tabrizi, Takahiro Shima, Shin Ichiro Takayanagi, Hiroaki Niiro, Ayano Yurino, Kohta Miyawaki, Katsuto Takenaka, Hiromi Iwasaki, Koichi Akashi, A TIM-3/Gal-9 Autocrine Stimulatory Loop Drives Self-Renewal of Human Myeloid Leukemia Stem Cells and Leukemic Progression, Cell stem cell, 10.1016/j.stem.2015.07.011, 17, 3, 341-352, 2015.09, Signaling mechanisms underlying self-renewal of leukemic stem cells (LSCs) are poorly understood, and identifying pathways specifically active in LSCs could provide opportunities for therapeutic intervention. T-cell immunoglobin mucin-3 (TIM-3) is expressed on the surface of LSCs in many types of human acute myeloid leukemia (AML), but not on hematopoietic stem cells (HSCs). Here, we show that TIM-3 and its ligand, galectin-9 (Gal-9), constitute an autocrine loop critical for LSC self-renewal and development of human AML. Serum Gal-9 levels were significantly elevated in AML patients and in mice xenografted with primary human AML samples, and neutralization of Gal-9 inhibited xenogeneic reconstitution of human AML. Gal-9-mediated stimulation of TIM-3 co-activated NF-κB and β-catenin signaling, pathways known to promote LSC self-renewal. These changes were further associated with leukemic transformation of a variety of pre-leukemic disorders and together highlight that targeting the TIM-3/Gal-9 autocrine loop could be a useful strategy for treating myeloid leukemias.. |
| 5. |
Yoshikane Kikushige, Fumihiko Ishikawa, Toshihiro Miyamoto, Takahiro Shima, Shingo Urata, Goichi Yoshimoto, Yasuo Mori, Tadafumi Iino, Takuji Yamauchi, Tetsuya Eto, Hiroaki Niiro, Hiromi Iwasaki, Katsuto Takenaka, Koichi Akashi, Self-Renewing Hematopoietic Stem Cell Is the Primary Target in Pathogenesis of Human Chronic Lymphocytic Leukemia, Cancer Cell, 10.1016/j.ccr.2011.06.029, 20, 2, 246-259, 2011.08, We report here that in chronic lymphocytic leukemia (CLL), the propensity to generate clonal B cells has been acquired already at the hematopoietic stem cell (HSC) stage. HSCs purified from patients with CLL displayed lymphoid-lineage gene priming and produced a high number of polyclonal B cell progenitors. Strikingly, their maturation into B cells was restricted always to mono- or oligo-clones with CLL-like phenotype in xenogeneic recipients. These B cell clones were independent of the original CLL clones because they had their own immunoglobulin VDJ genes. Furthermore, they used preferentially VH genes frequently used in human CLL, presumably reflecting the role of B cell receptor signaling in clonal selection. These data suggest that HSCs can be involved in leukemogenesis even in mature lymphoid tumors.. |
| 6. |
Yoshikane Kikushige, Takahiro Shima, Shin-ichiro Takayanagi, Shingo Urata, Toshihiro Miyamoto, Hiromi Iwasaki, Katsuto Takenaka, Takanori Teshima, Toshiyuki Tanaka, Yoshimasa Inagaki, Koichi Akashi, TIM-3 is a promising target to selectively kill acute myeloid leukemia stem cells, Cell Stem Cell, 10.1016/j.stem.2010.11.014, 7, 708-717, 2010.12. |
